Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7SY3BN)

DOT Name Transcription factor ATOH8 (ATOH8)
Synonyms Class A basic helix-loop-helix protein 21; bHLHa21; Helix-loop-helix protein hATH-6; hATH6; Protein atonal homolog 8
Gene Name ATOH8
Related Disease
Anemia ( )
Beta thalassemia ( )
Colorectal carcinoma ( )
Hepatitis B virus infection ( )
Hepatocellular carcinoma ( )
Lung adenocarcinoma ( )
Neoplasm ( )
Pulmonary arterial hypertension ( )
Teratoma ( )
Advanced cancer ( )
UniProt ID
ATOH8_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF00010
Sequence
MKHIPVLEDGPWKTVCVKELNGLKKLKRKGKEPARRANGYKTFRLDLEAPEPRAVATNGL
RDRTHRLQPVPVPVPVPVPVAPAVPPRGGTDTAGERGGSRAPEVSDARKRCFALGAVGPG
LPTPPPPPPPAPQSQAPGGPEAQPFREPGLRPRILLCAPPARPAPSAPPAPPAPPESTVR
PAPPTRPGESSYSSISHVIYNNHQDSSASPRKRPGEATAASSEIKALQQTRRLLANARER
TRVHTISAAFEALRKQVPCYSYGQKLSKLAILRIACNYILSLARLADLDYSADHSNLSFS
ECVQRCTRTLQAEGRAKKRKE
Function
Transcription factor that binds a palindromic (canonical) core consensus DNA sequence 5'-CANNTG- 3' known as an E-box element, possibly as a heterodimer with other bHLH proteins. Regulates endothelial cell proliferation, migration and tube-like structures formation. Modulates endothelial cell differentiation through NOS3. May be implicated in specification and differentiation of neuronal cell lineages in the brain. May participate in kidney development and may be involved in podocyte differentiation. During early embryonic development is involved in tissue-specific differentiation processes that are dependent on class II bHLH factors and namely modulates the differentiation program initiated by the pro-endocrine factor NEUROG3. During myogenesis, may play a role during the transition of myoblasts from the proliferative phase to the differentiation phase. Positively regulates HAMP transcription in two ways, firstly by acting directly on the HAMP promoter via E-boxes binding and indirectly through increased phosphorylation of SMAD protein complex. Repress NEUROG3-dependent gene activation in a gene-specific manner through at least two mechanisms; requires only either the sequestering of a general partner such as TCF3 through heterodimerization, either also requires binding of the bHLH domain to DNA via a basic motif.
Tissue Specificity Expressed in lung, liver, kidney, heart and pancreas. Expressed in endothel of umbilical vessels.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Anemia DISTVL0C Strong Altered Expression [1]
Beta thalassemia DIS5RCQK Strong Altered Expression [1]
Colorectal carcinoma DIS5PYL0 Strong Altered Expression [2]
Hepatitis B virus infection DISLQ2XY Strong Biomarker [3]
Hepatocellular carcinoma DIS0J828 Strong Posttranslational Modification [3]
Lung adenocarcinoma DISD51WR Strong Altered Expression [4]
Neoplasm DISZKGEW Strong Altered Expression [5]
Pulmonary arterial hypertension DISP8ZX5 Strong Biomarker [6]
Teratoma DIS6ICY4 Strong Biomarker [3]
Advanced cancer DISAT1Z9 Limited Biomarker [5]
------------------------------------------------------------------------------------
⏷ Show the Full List of 10 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Transcription factor ATOH8 (ATOH8). [7]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Transcription factor ATOH8 (ATOH8). [17]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Transcription factor ATOH8 (ATOH8). [19]
------------------------------------------------------------------------------------
12 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Transcription factor ATOH8 (ATOH8). [8]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Transcription factor ATOH8 (ATOH8). [9]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Transcription factor ATOH8 (ATOH8). [10]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Transcription factor ATOH8 (ATOH8). [11]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Transcription factor ATOH8 (ATOH8). [12]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Transcription factor ATOH8 (ATOH8). [13]
Fluorouracil DMUM7HZ Approved Fluorouracil affects the expression of Transcription factor ATOH8 (ATOH8). [14]
Troglitazone DM3VFPD Approved Troglitazone decreases the expression of Transcription factor ATOH8 (ATOH8). [15]
Pantothenic acid DM091H2 Approved Pantothenic acid increases the expression of Transcription factor ATOH8 (ATOH8). [16]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide increases the expression of Transcription factor ATOH8 (ATOH8). [18]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Transcription factor ATOH8 (ATOH8). [20]
Sulforaphane DMQY3L0 Investigative Sulforaphane decreases the expression of Transcription factor ATOH8 (ATOH8). [21]
------------------------------------------------------------------------------------
⏷ Show the Full List of 12 Drug(s)

References

1 Hepcidin suppression in -thalassemia is associated with the down-regulation of atonal homolog 8.Int J Hematol. 2017 Aug;106(2):196-205. doi: 10.1007/s12185-017-2231-3. Epub 2017 Apr 12.
2 High expression of atonal homolog 8 predicts a poor clinical outcome in patients with colorectal cancer and contributes to tumor progression.Oncol Rep. 2017 May;37(5):2955-2963. doi: 10.3892/or.2017.5554. Epub 2017 Apr 5.
3 Loss of ATOH8 Increases Stem Cell Features of Hepatocellular Carcinoma Cells.Gastroenterology. 2015 Oct;149(4):1068-81.e5. doi: 10.1053/j.gastro.2015.06.010. Epub 2015 Jun 20.
4 Integrated transcriptomics reveals master regulators of lung adenocarcinoma and novel repositioning of drug candidates.Cancer Med. 2019 Nov;8(15):6717-6729. doi: 10.1002/cam4.2493. Epub 2019 Sep 10.
5 DNA methylation changes involved in the tumor increase in F2 males born to gestationally arsenite-exposed F1 male mice.Cancer Sci. 2019 Aug;110(8):2629-2642. doi: 10.1111/cas.14104. Epub 2019 Jul 25.
6 The ALK-1/SMAD/ATOH8 axis attenuates hypoxic responses and protects against the development of pulmonary arterial hypertension.Sci Signal. 2019 Nov 12;12(607):eaay4430. doi: 10.1126/scisignal.aay4430.
7 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
8 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
9 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
10 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
11 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
12 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
13 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
14 Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer. BMC Genomics. 2006 Apr 3;7:68. doi: 10.1186/1471-2164-7-68.
15 Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
16 Calcium pantothenate modulates gene expression in proliferating human dermal fibroblasts. Exp Dermatol. 2009 Nov;18(11):969-78. doi: 10.1111/j.1600-0625.2009.00884.x. Epub 2009 Apr 8.
17 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
18 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
19 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
20 Identification of gene markers for formaldehyde exposure in humans. Environ Health Perspect. 2007 Oct;115(10):1460-6. doi: 10.1289/ehp.10180.
21 Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.